Alcohol consumption and its sequellae are major risk factors associated with bacterial infection. Previously, we have shown that acute intoxication interferes with PMN adhesion and delivery, and that settings of chronic drinking can be associated with poor chemotaxis. PMN function will be studied in 3 contexts: 1. Alcohol-induced inhibition of adhesion to endothelium - cultured endothelial monolayers will be used for measuring PMN adhesion. The significance of ligand binding reactions to normal PMN-endothelial interaction will be assessed as well as the effect of ethanol on that reaction. The contribution of other whole blood elements and of humoral factors to alcohol's inhibition of adhesion will be studied. Alcohol's direct effect on morphology and function of endothelial cells be assessed. 2. PMN function in spur-cell anemia - the cellular basis for the impaired adhesion and movement of PMNs in this condition will be evaluated. Their plasma membranes will be isolated to measure cholesterol:phospholipid content and adhesion to normal endothelial cells. Adhesion of spur-cell PMNs to endothelim in the presence and absence of alcohol, as well as functions such as deformability, membrane "fluidity", and cytotoxicity will be measured. Cholesterol-rich liposomes will be used to modify plasma membrane cholesterol content of PMNs and endothelial cells, and an attempt will be made to study endothelial cells from spur-cell animals. The goal of these studies is an understanding of the pathogenesis of poor PMN function in this syndrome, and insight into the importance of lipid content to PMN function. 3. Correlations between clinical alcoholic liver disease, lipid metabolism, and PMN function - patients with alcoholic cirrhosis and those admitted for withdrawal from alcohol will be studied to correlate various liver parameters, serum lipids, and PMN functions. These patients will have measurement of liver injury, serum and PMN membrane lipid composition, in vitro PMN function tests, and in vivo delivery into skin window inflammatory sites. The goal is to determine which in vitro measurements predict poor PMN delivery in vivo. The findings of the proposed experiments should provide better understanding of the pathogenesis of poor PMN host defense in alcoholism, and suggest more effective ways to prevent and treat infections associated with alcoholism.